A stromal niche regulate CSCs in Wnt-Met mammary gland tumors. Mus musculus

CSCs may be regulated by extrinsic signals provided by specialized microenvironments, or niches, which sustain CSC expansion. We investigated the role of cancer associated fibroblasts (CAFs) in the regulation of CSCs using a genetically engineered mouse model of basal-like breast cancer driven by combined activation of Wnt/β-catenin and HGF/Met signaling (Wnt-Met mice). We found that CAFs secrete soluble factors that promote the expansion of the population of self-renewing cells that generate mammospheres and enhance the capacity of CSCs to form invasive 3D structures. Using transcriptional profiling, we identified a network of paracrine interactions between CAFs and CSCs that regulate reciprocal functions. Overall design: We sorted CAFs, CSCs and TECs from Wnt-Met mammary gland tumors and fibroblasts from control mammary glands (COFs). We performed microarray analysis on RNA samples isolated from sorted cells to evaluate gene differentially expressed between CAFs and COFs, CSCs and TECs, and potential interactions that CAFs and CSCs establish in Wnt-Met mammary gland tumors